Similarity and difference between systemic lupus erythematosus and NZB/W F1 mice by multi-omics analysis.

OBJECTIVES: Several animal disease models have been used to understand the mechanisms of systemic lupus erythematosus (SLE), however, translation of findings from animals to humans has not been sufficiently examined in drug development. To confirm the validity of NZB/W F1 mice as an SLE model, we extensively characterized SLE patients and NZB/W F1 mice by omics analysis.

METHODS: Peripheral blood from patients and mice, and spleen and lymph node tissue from mice were analyzed using cell subset analysis, cytokine panel assays and transcriptome analysis.

RESULTS: CD4+ effector memory T cells, plasmablasts and plasma cells were increased in both SLE patients and NZB/W F1 mice. Levels of TNF-α, IP-10 and BAFF in plasma were significantly higher in SLE patients and NZB/W F1 mice than in their corresponding controls. Transcriptome analysis revealed an upregulation of genes involved in the interferon signaling pathway and T cell exhaustion signaling pathway in both SLE patients and the mouse model. In contrast, death receptor signaling genes showed changes in opposite direction between patients and mice.

CONCLUSIONS: NZB/W F1 mice are a generally suitable model of SLE for analyzing the pathophysiology and treatment response of T/B cells and monocytes/macrophages, and their secreted cytokines.